Summary of work: Osteoarthritis (OA) is the most common form of arthritis in the elderly, and is a major cause of activity limitation, physical disability and health services utilization in the elderly. As part of the ongoing studies of OA in the Baltimore Longitudinal Study of Aging (BLSA), in order to test the hypothesis that genetic markers may be implicated in the expression of OA, especially generalized (polyarticular) OA, we have examined the association between alleles of the polymorphic human aggrecan gene (at least 11 alleles identified) and bilateral hand and knee OA in 74 Caucasian men aged 60 and over. After adjustment for differences in age and obesity, we found that men who have one of the most common alleles of this aggrecan gene have a five-fold greater likelihood of having moderate to severe hand OA in multiple joints on both hands. The genetic studies have also been investigated using an epidemiological approach. We have been studying the familial association of hand OA and of generalized OA (OA in multiple hand joints plus knees) in the family members among the BLSA participants. We found that the presence of OA in each of the hand joints, in multiple hand joint sites, and generalized OA, were all more highly correlated among brothers, sisters, and in sister-brother pairs, than among unrelated people. The clinical implications of the radiographic findings of OA have been investigated by examining the association among pain reporting, personality, and radiographic knee OA, using different measures of musculo-skeletal symptoms (AIMS, NHANES-I arthritis supplement), of disability and function, and personality profiles (NEO) in the BLSA subjects, in order to further understand why some people with radiographic knee OA have pain while others do not, and why some report pain with no radiographic OA. Early results of the analysis of the AIMS data show that anxiety and depression scores are higher in men and women who report pain, but who have no x-ray evidence of OA, suggesting that anxiety and depression are risk factors for the reporting of pain in the absence of radiographic OA.